Genital infections are one of the major causes of tubal infertility in humans. Infertility secondary to tubal damage is a health problem that results in significant human suffering and an enormous economic burden. the overall objective of this proposal is to determine if a vaccine can prevent tubal infertility secondary to a Chlamydia trachomatis infection. The major outer membrane protein (MOMP) of C. trachomatis, a protein that has been found to be strongly antigenic and to elicit neutralizing antibodies, will be used for vaccination. Infertility secondary to a chlamydial infection is thought to be primarily due to the immunopathological reaction of the host to the infection and not to damage produced by the bacterial pathogen itself. Thus, characterization of the immunopathology of the infection in control and experimental animals should help us to construct a more effective vaccine. Here, the C. trachomatis mouse pneumonitis (MoPn) salpingitis model will be used to study tubal infertility. In this model, female mice injected in the ovarian bursae with elementary bodies of C. trachomatis MoPn develop infertility as a sequelae to the acute salpingitis episode. Female BALB/c mice will be vaccinated with MOMP, challenged with C. trachomatis MoPn infectious elementary bodies in the ovarian bursae, and their fertility rates compared with that of control non-vaccinated mice. Assuming that the animals vaccinated with MOMP have a higher fertility rate we will then proceed to define what domains of the MOMP account for the protection. To determine what regions of the MOMP are immunogenic, overlapping synthetic peptides will be used to map those epitopes that elicit a protective B- and T-cell response. The systemic and local humoral and cell-mediated immune response will be determined in both groups of mice by measuring immunoglobulin levels in serum and vaginal secretions, cellular ELISA and lymphocyte proliferation assays, and the footpad swelling test. In addition, the infection will be followed by culture, immunofluorescence and DNA amplification. Light and electron microscopy will be performed to assess the host defense immune-mechanisms at the tissue level. Based on these results, peptides will be made to different regions of the MOMP and will be tested as vaccines for their ability to preserve fertility. Once these domains of the MOMP have been defined, and their immunogenic activity characterized, a recombinant subunit vaccine will be constructed and tested for its ability to protect mice against C. trachomatis MoPn induced infertility.